title: Advances in adenovirus-mediated p53 cancer gene therapy.
abstract: BACKGROUND
  The tumor suppressor p53 gene regulates diverse cellular processes, such as cell-cycle arrest, senescence, apoptosis and autophagy, and it is frequently inactivated by genetic alterations in ∼ 50% of all types of human cancers. To restore wild-type p53 function in p53-inactivated tumors, adenovirus-mediated p53 gene therapy has been developed as a promising antitumor strategy in preclinical experiments and clinical studies.
  
  
  METHODS
  This review focuses on the clinical relevance of replication-deficient adenovirus vectors that carry the wild-type p53 gene (Ad-p53; Advexin, Gendicine and SCH-58500) in clinical studies of patients with various cancers and the future perspectives regarding conditionally replicating adenovirus vectors expressing the wild-type p53 gene (CRAd-p53; AdDelta24-p53, SG600-p53, OBP-702) in preclinical experiments. Moreover, the recent advances in our understanding of the molecular basis for the p53-mediated tumor suppression network induced by Ad-p53 and CRAd-p53 vectors and the combination therapies for promoting the therapeutic potential of adenovirus-mediated p53 gene therapy are discussed.
  
  
  CONCLUSIONS
  Exploration of the molecular mechanism underlying the p53-mediated tumor suppression network and the effective strategy for enhancing the p53-mediated cell death signaling pathway would provide novel insights into the improvement of clinical outcome in p53-based cancer gene therapy.
authors.affiliation: Okayama University Hospital, Center for Innovative Clinical Medicine , Okayama 700-8558 , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kagawa
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000502:physiology; D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000502:physiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D024201:Bystander Effect; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
chemical_list: D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D035683:MicroRNAs; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53